Neurosciences Commons^™

Completing The Puzzle: Why Studies In Non-Human Primates Are Needed To Better Understand The Effects Of Non-Invasive Brain Stimulation, Sebastian J. Lehmann, Brian D. Corneil

Brain and Mind Institute Researchers' Publications

Brain stimulation is a core method in neuroscience. Numerous non-invasive brain stimulation (NIBS) techniques are currently in use in basic and clinical research, and recent advances promise the ability to non-invasively access deep brain structures. While encouraging, there is a surprising gap in our understanding of precisely how NIBS perturbs neural activity throughout an interconnected network, and how such perturbed neural activity ultimately links to behaviour. In this review, we will consider why non-human primate (NHP) models of NIBS are ideally situated to address this gap in knowledge, and why the oculomotor network that moves our line of sight offers …

Learning Words Without Trying: Daily Second Language Podcasts Support Word Form Learning In Adults, Elise Alexander, Stephen C. Van Hedger, Laura Batterink

Brain and Mind Institute Researchers' Publications

Spoken language contains overlapping patterns across different levels, from syllables to words to phrases. The discovery of these structures may be partially supported by statistical learning (SL), the unguided, automatic extraction of regularities from the environment through passive exposure. SL supports word learning in artificial language experiments, but few studies have examined whether it scales up to support natural language learning in adult second language learners. Here, adult English speakers (n = 70) listened to daily podcasts in either Italian or English for two weeks while going about their normal routines. To measure word knowledge, participants provided familiarity ratings of …

The Importance Of Protein Context In Spinocerebellar Ataxia Type 3, Sean Luis Johnson

Wayne State University Dissertations

Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington's Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside …

Investigating The Relationship Between Biological Age And Mutant Huntingtin Misfolding, Ratnesh Kesineni

Honors Undergraduate Theses

Huntington Disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG trinucleotide repeat tract in the huntingtin (HTT) gene. This CAG tract expansion causes production of mutant HTT (mtHTT) protein, which misfolds and forms inclusions in the brain that accumulate with age. Misfolded mtHTT aggregates have been linked with increased cell death in neuron cell culture, leading to speculation that mtHTT aggregates cause cell death. However, there are mouse lines that have robust mtHTT inclusion deposition, but no HD-like signs or neurodegeneration. Furthermore, neuronal HD cultured cells with inclusions were found to be …

Backward Walking: A Novel Marker Of Fall Risk, Cognitive Dysfunction, And Myelin Damage In Persons With Multiple Sclerosis, Erin Edwards

Wayne State University Dissertations

Multiple sclerosis (MS) is a progressive, neurologic disease of the central nervous system that causes debilitating motor, sensory and cognitive impairments. As a result, persons with MS are at an increased risk for falls and falls represent a serious public health concern for the MS population. The current clinical measures used to assess fall risk in MS patients lack sensitivity and predictive validity for falls and are limited in their ability to capture to multiple functional domains (i.e., motor, sensory, cognitive and pathological domains) that are impaired by MS. Backward walking sensitively detects falls in the elderly and other neurologic …

Dancing The Storm: Neurobiological Correlates Of Trauma-Related Psychopathology In Youth Resettled As Refugees, And The Efficacy Of Creative Arts And Movement Therapies To Address Trauma-Related Psychopathology, Lana Ruvolo Grasser

Wayne State University Dissertations

Exposure to stress and trauma activates key adaptive pathways, including the sympathetic adrenomedullary system and the immune system, which can result in long-term health impacts of trauma especially when experienced during sensitive developmental periods. Alterations in these systems are measurable through non-invasive methods including skin conductance response (SCR), fear potentiated startle (FPS), and inflammation. Research regarding the impact of trauma, and more specifically posttraumatic stress disorder, has primarily focused on adults, and there is a paucity of neurobiological research in displaced populations—like refugees—who may experience higher rates of trauma exposure and related psychopathology. The present study measured SCR to a …

Crispr-Krispr: A Method To Identify On-Target And Random Insertion Of Donor Dnas And Their Characterization In Knock-In Mice, Masayuki Tanaka, Keiko Yokoyama, Hideki Hayashi, Sanae Isaki, Kanae Kitatani, Ting Wang, Hisako Kawata, Hideyuki Matsuzawa, Channabasavaiah B. Gurumurthy, Hiromi Miura, Masato Ohtsuka

Journal Articles: Pharmacology & Experimental Neuroscience

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.

Ecdysoneless Overexpression Drives Mammary Tumorigenesis Through Upregulation Of C-Myc And Glucose Metabolism, Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band

Journal Articles: Pharmacology & Experimental Neuroscience

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition …

Efficacy Of Prebiotic Dietary Intervention To Mitigate Risks For Dementia Via The Gut-Brain Axis, Lucille M. Yanckello

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia with various risk factors including age, environmental factors such as brain injury and genetic factors, such as the E4 allele of the Apolipoprotein gene. Presence of the APOE4 allele increases AD risk by two- to four- fold. Recent studies have shown that mild traumatic brain injury (mTBI), even without loss of consciousness, increases risk of dementia diagnosis by more than two-fold in military personnel and is also a significant environmental risk factor for developing dementia in the general population. The gut-brain axis (GBA) or bi-directional communication between the brain and …

The Role Of Socioeconomic Status In Cognition And Brain Health Across The Lifespan, Erica Chung

Honors Theses

Disparities in cognition are inevitable throughout the lifespan due to socioeconomic gaps. Individuals of lower socioeconomic status (SES) may have fewer access to environmental resources, especially with regard to education, than individuals of higher socioeconomic status. Differences in available resources from a young age may affect brain development, leading to detriments in cognition and behavior, further impacting socioeconomic success in adulthood. In the present study, we modeled the development of the dorsolateral prefrontal cortex (DLPFC) and changes in cognitive function throughout the life trajectory in the Nathan Kline Institute for Psychiatric Research Rockland Sample. The DLPFC volume was predicted to …

The Anorexic Effect Of Dl-Fenfluramine Is Dependent On Animals' Habituation To Different Food Types, Sun Shin Yi, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Background: As rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard …

A Study Of Limited Bedding And Nesting On Maternal Behavior For Postpartum Depression, Emma Brezoczky

CMC Senior Theses

Postpartum depression (PPD) affects up to 20% of mothers in the US and can detrimentally affect both the mother and psychosocial development of the child (Pearlstein et al, 2009). So far, research on PPD is limited and the underlying neuropathology remains unclear. Low socioeconomic status is one risk factor that increases the risk of PPD tenfold (Goyal et al, 2010). The low resource limited bedding and nesting (LBN) paradigm used for rodents has the potential to model this risk factor. LBN has not previously been studied with PPD, but observations of disrupted maternal behaviors and depressive phenotypes makes it a …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Mental Disorders, The Positivity Effect, And Questions Of Identity And Responsibility, Liam Jones

Pitzer Senior Theses

In order to judge how behavior caused by the positivity effect should be considered, comparisons were made between the positivity effect and two mental disorders. These disorders, Tourette’s syndrome and psychopathy, were selected due to their extreme differences in what Strawsonian attitudes they inspire and how they are perceived relative to disordered patients’ will. Disorder-affected behavior of Tourette’s patients inspires the objective attitude and is seen as a condition affecting an individual’s will, while disorder-affected behavior of psychopaths inspires the interpersonal attitude and is seen as a character trait. Relevant distinctions between psychopathy and Tourette’s syndrome were found to include …

The Effect Of Young Blood Anti-Aging Treatment On Protein Markers Of Age And Huntington Disease, Sujena H. Koilpillai

Honors Undergraduate Theses

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract within the huntingtin (HTT) protein, forming mutant HTT (mtHTT). HD patients suffer from psychiatric, behavioral, cognitive, and motor abnormalities, with death typically occurring 15-20 years after symptom onset. Currently, there are no treatments able to slow disease progression or delay onset. HD is a disease of aging. Despite the mtHTT protein being produced throughout life, symptoms do not typically appear until adulthood. Furthermore, many cellular effects of normal aging are also seen in HD, including altered intercellular communication and loss of proteostasis. Recently, our lab found …

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond

Theses and Dissertations--Neuroscience

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.

We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …